Curs_6 Semnalizarea Celulara

Semnalizarea celulara Curs 6

Transcript of Curs_6 Semnalizarea Celulara

  • Semnalizarea celularaCurs 6

  • Cell SignalingCelulele primesc si trimit informatii (semnale) Celulele simt si raspund schimbarilor din mediu deciSemnalele provin din interiorul celulei, de la alte celule sau din mediu

  • Generic Signaling PathwaySignalReceptor (sensor)

    Transduction Cascade

    OutputSomethinghappensoutsideinside (cytosol)

  • Raspunsul la semnalizarea celularaExprimarea genelor este modificata la nivelul transcrierii, a procesarii ARN sau a translatieiModificarea activitatii enzimaticeInteractiile proteina-proteina sunt induse sau inhibateSe schimba localizarea unor proteine sau a altor componenete celulareModificari biochimice

  • Raspunsul la semnalizarea celularaCelula:Se divide sau se inceteaza diviziuneaSe diferentiazaSe sinucide sau omoara pe cinevaSe misca sau se opreste Isi modifica metabolismulIgnora semnalulModificari fiziologice

  • Natura semnalului

    Peptide - insulina, glucagon...ProteineDerivati din aac - histaminaBiomolecule mici - ATPSteroizi, Gaze - (NO)FotoniADN degradat

  • Cell respond to external signals

    = A signaling molecule binds to a receptor protein, causing to change shape

    = transduction: cascades of molecular interactions = Response: signaling leads to regulation of transcription or cytoplasmatic activities = signal transduction pathways

  • Signaling cascades have many stepsPast:EnumeratecomponentsNow: Modules Circuits/ Design Logic Cross-talk Specificity

  • Signaling molecules operate over various distances in animals-extracellular signaling can occur over:1. large distances or endocrine signaling signaling molecules are called hormones- act on target cells distant from their site of synthesis-usually carried through the bloodstream2. short distances or paracrine signaling affects target cells within proximityto the cell that synthesized the molecule-usually mediated by neurotransmitters and some growthfactors

  • Steroid Hormone Signaling PathwaySignal (steroid)

    Receptor (txn factor)

  • Steroid Hormone Signaling PathwayOutput gene expression cell physiology

  • Adrenaline signalingSignal: Adrenaline (epinephrine)Secreted by adrenal gland

    Receptor: b-adrenergic receptor

    Response:Breakdown of glycogen to glucose to provide energy for fight-or-flight

  • Insulin signalingSignal: insulinSecreted by b cells of pancreasReceptor: a receptor kinaseResponse:Sugar is taken up from bloodstream into cellsDiabetes - type 1, type 2

  • Growth factor signaling

  • The growth of multicellular organisms is regulated by more than just nutrient availabilityNUTRIENTSunicellulareukaryotemulticellulareukaryote

  • Cells in multicellular eukaryotes require permission signals from growth factorsNUTRIENTS

  • Disregulation of growth factor signal transduction leads to cancerNUTRIENTScellulartransformation

  • Some growth factorsEGF - epidermal growth factorFGF - fibroblast growth factorNGF - nerve growth factorPDGF - platelet-derived growth factorInsulin-like GF

    All of these bind to a class of receptors known as Receptor Kinases

  • Receptors with enzymatic activity

  • Protein kinases and phosphatases- Add/remove phosphates to/from proteins- Involved in all signaling from cell surface receptors, and in most other signaling too

  • Protein Kinase ReactionSubstrate

  • Phosphorylation of protein substratesProtein Kinase ReactionProduct

  • Phosphorylation can flip a protein from active to inactive or vis-versaATPADP

    Dont worry about the all these ovals, if you know that Raf-1 activates the MAPK pathway and that MAPKs activate transcription of certain target genes, I will be happyAlso note an instance of crosstalkRas activates PI3K and you can bet that I will be talking about the PI3K pathway later b/c thats what I work on!Mammalian cells still have the ability to sense extracellular conditions and respond, but perhaps less important in the relative safety of a mutlicellular organism. However, mammalian cells are under an extra level of control . . .Energy in high energy phosphate bonds used to regulate reactions, 2 different mechanisms